N-(1-indanyl)-n&#39;-(beta-substituted ethyl)-ureas



Barry M. Bloom, Jackson Heights, N.Y., assignor to Chas. Pfizer & Co., Inc.,Brooklyn, N.Y., a corporation of v Delaware No Drawing. Original application July 8, 1957, Serial No. 670,373. Divided and this application July 10, 1958, Serial No. 750,060

7 Claims. (Cl. 260-456) This application is concerned with new and useful therapeutic agents. In particular, it is concerned with compounds which are effective regulators of the central nervous system, being especially useful as tranquilizing agents. This application is a divisional application of application Serial No. 670,373 of July 8, 1957.

' The compounds of this invention are substituted and natively, the products are prepared by the reaction between a l-indanyl isocyanate and an alkylamine with similar substituents in a position 5 to the amine group. Thus it is possible to prepare N-(l-indanyl)-N'-/3-brom'oethy1 urea by the reaction between l-indanylamine and fi-bromoethyl isocyanate or by the reaction between l-indanyl isocyanate and fl-bromoethylamine. In either case 2-(1- indanylarnino)-oxazoline is prepared from the urea by the elimination of hydrogen bromide. The reactions are shown below.

(1)v a gamma. i

1 :11. NHooNHomomBr A HBr N NHICONHOHICHIBX' I N-o (2) i Bl'CHsCHzNH: (I; 1 10 o irnooNnornornnr HBI N l NHCONHCHzCHzBr r a Iii o i In the reaction shown above, the fi-substituted alkylamine and isocyanate are bromoethyl compounds and 2,883,410v Patented Apr. 21, 1959 2 the oxazoline prepared is unsubstituted on both of the methylene groups. By choice of the proper amine or isocyanate it is possible to prepare oxazolines with one of both of the methylene groups either monosubstituted or disubstituted. It is, therefore, also intended to include within the purview of this invention oxazolines in which either or both of the methylene groups are substituted with at least one alkyl group containing up to four carbon atoms, the total number of carbon atoms in these substituents being from one to eight. As an example of the preparation of this type of compound, 2-(1-indanylamino)-5-ethyloxazoline can be prepared by reacting l-indanylamine with fi-bromobutyl isocyanate and sub-v sequently heating.

For the preparation of the active urea compounds of this invention, the bromine of the above reaction may be replaced with other halogens such as chlorine or iodine, or with alkyl or aryl sulfonyl groups such as methanesulfonyloxy or p-toluenesulfonyloxy. In these cases, the active oxazoline is formed by the elimination of hydrogen chloride, hydrogen iodide, methanesulfonic acid and p-toluenesulfonic acid respectively. Since the amino-oxazolines are basic in nature the liberated acid, which has been eliminated from the urea compound, adds to it to form an acid addition salt. The free base may be liberated from the acid addition salt using an alkaline reagent such as ammonium hydroxide, sodium hydroxide, sodium bicarbonate, calcium oxide and other obvious equivalents.

The hydrogen atoms of the indanyl group in the above reactions may be replaced with certain substituents to reduce or enhance the therapeutic effect of the unsubstituted compounds. These substituents include from one to three alkyl groups, alkoxy groups and thioalkyl groups containing up to four carbon atoms, as well as from one to three chloride, bromine or iodine atoms.

The a and 5 carbon atoms of the ethyl portion of the N-(l-indanyl)-N-([i-substituted ethyl)-ureas which are themselves therapeutically active and can also be used for the preparation of the active oxazolines of the present invention may be substituted with alkyl groups containing from one to four. carbon atoms, the total number of substituent carbon atoms being from one to eight. The compound which will give 2-(1-indanylamino)-4,4,5,5- tetraethyloxazoline is N-(l-indanyl)-N-(a,a,p,fl-tetra ethyl-fl-halo)-ethyl urea. Similarly, N-(1-indanyl)-N- (u,a-dibutyl-,6-halo)-ethyl urea and N-(l-indanyl)-N- (a,;8-dibutyl-fi-halo)-ethy1 urea will yield respectively 2- (l-indanylamino)-4,4-dibutyl oxazoline and Z-(I-indanylamino)-4,5-dibutyl oxazoline.

The following list is illustrative of compounds of this invention.

N (2,5 dithiomethyH-indanyl)-N'-(a-methyl-B-butylp-iodo)-ethyl urea.

N-(3,4-diethoxy-l-indanyl)-N-;3-chloroethy1 urea.

2- 2,3 -dichloro-1 -indanylamino) -oxazoline.

2- (2-bromo- 1 -indanylamino )-4-methyl-oxazo1ine. 2-(4-ethyl-1-indanylamino)-3,4-dimethy1-oxazoline.

2- (2,3 ,5 -triiodo-1-indanylamino) -oxazoline.

2- 3 ,4-dithiomethyll-indanylarnino -4-n-butyloxaz oline. 2 (2,3,5 tri-sec-butoxy-l-indanylamino)-4,5-diethyloxazoline.

2- 4-thio-tert-butyl- 1 -indanylamino) -oxazoline. 2-(2,3,5-trimethyl-l-indanylamino)-oxazoline.

2- (2,3 ,5 -trithiomethyll-indanylamino) -oxazoline. 2-(2,7-diethoxy-1-inda.nylamino) -4,5-dimethyl-oxazoline. 2- (4-thiois op ropyl- 1 -ind anylamino) -5' -ethyl-oxazoline.

The amines and isocyanates necessary for the preparation of the compounds of this invention are known, or can be prepared, by procedures well known in the art. The alkyl isocyanates, for example, are prepared by treatment of the corresponding acid chlorides with sodium azide. The alkylamines can be prepared utilizing the Hofmann on the corresponding amides. The l-indanylamines can be prepared from the corresponding l-indanones by conversion of the latter compounds to oximes and reduction, for example, with lithium aluminum hydride. If it should be desired to prepare a l-indanyl isocyanate, this can be accomplished by treating the amine with phosgene and warming the resulting carbamyl chloride to eliminate hydrogen chloride.

In carrying out the reaction the isocyanate and amine are contacted in benzene or in an equivalent aromatic solvent. Hydrocarbon solvents, both aromatic and aliphatic can be used. Halogenated and nitrated hydrocarbon solvents are also useful. There may be mentioned by way of example, chloroform, carbon tetrachloride, ethylene dichloride, chlorobenzene, toluene, xylene, nitrobenzene and nitrotoluene. Lower oxygenated aliphatic solvents, particularly ethers containing up to eight carbon atoms are particularly useful.

The reaction between an amine and an isocyanate generally takes place without the application of heat. In fact, with some of the more reactive compounds, it is best to carry out the reaction in an ice bath. However, as in other reactions of this type, the progress of the reaction may be hastened by the use of heat. With certain of the more inactive reactants, it may even :be necessary to apply heat. It has been found that temperatures from 0 to 110 C. are useful and that most of the amines and isocyanates react to form products of this invention below 50 C.

Formation of an oxazoline acid addition salt by the elimination of an acid from the urea compound is best carried out in refluxing aqueous solution although lower alkanols such asmethanol, ethanol, propanol or butanol may be used.

Although both reactions of the synthesis proceed readily at atmospheric pressure, for certain applications it may be desirable to use increased pressure. Pressures as high as 100 atmospheresmay be useful.

The compounds of this invention are useful as central nervous system depressants and when administered to rodents, it is found that they significantly reduce the spontaneous motility of these animals. Similar results are observed with monkeys and other higher animals.

It is a most unexpected finding in view of the aliphatic nature of the l-indanyl group to discover that ureas and aminooxazolines substituted with these groups have central nervous system regulatory activity. Copending patent application, Serial No. 587,224, filed May 25, 1956, now Patent No. 2,811,529, describes certain naphthyl ureas and naphthylaminooxazolines which have this type of activity. It should be noted that the naphthyl ring described in said copending application is a fully aromatic ring and, therefore, the groups attached to the ring should manifest chemical and physiological reactions associated with aromaticity. 0n the other hand, substituents attached to the 1-position of I-indanyl groups should manifest chemical and physiological reactions associated with aliphatic activity. It is well known that benzyl substituted ureas and oxazolines do not have central nervous system regulatory action despite the fact that, as in the l-indanyl compounds of the present invention, groups attached to the methylene moiety are aliphatic in nature. It is apparent then that it is most unexpected, and certainly not predictable, to find that the aliphatic compounds of the instant invention have activity similar to the aromatic compounds of the prior invention especially when it is known that other aliphatic analogs do not have this activity.

Each of the types of compounds of this invention has its own specific advantages. For example, although both the ureas and the oxazolines are effective therapeutically, the oxazolines produce their effect in a shorter time. On the other hand, the ureas, while they require a somewhat longer time to take their effect, are less toxic and can, therefore, be administered in larger dosages. This suggests that under certain circumstances it may be advantageous to administer both agents simultaneously to produce both a rapid and a prolonged therapeutic action.

The ureas are neutral and do not form the acid addition salts. The oxazolines, however, are weakly basic and do form acid addition salts. These salts because of their water solubility, are more readily utilizable for the preparation of aqueous parenteral solutions than are the free 1.

bases.

With reference to the oxazolines of this invention, it is specifically intended to include within the purview of the invention the acid addition salts which these compounds form with acids having pharmaceutically acceptable anions. The term, pharmaceutically acceptable anion has a definite meaning to one skilled in the art. It is defined as a non-toxic anion of any of the simple acids commercially used therapeutically to neutralize basic medicinal agents when the salt thereof is to be administered to a human host. These acids include, for example, hydrochloric, hydrobromic, hydriodic, sulfuric, succinic, maleic, tartaric, citric, glycolic and others. The pharmaceutical activity of the molecule is primarily a function of the cation, the anion serving chiefly to supply electric neutrality.

By reference to the reaction described above, it can be seen that in the oridinary practice of the process of the invention, the oxazolines produced will be hydrobromides, hydrochlorides, hydriodides, methanesulfonic acids or ptoluenesulfonic acids. These acids can be converted to other pharmaceutically acceptable acids by procedures we'll known to those skilled in the art. One highly useful method comprises contacting the acid addition salt with a basic anion exchange resin, for example, a highly basic compound such as the one available from Rohm & Haas Company under the name Amberlite IRA-400. This resin is a polyquaternary ammonium compound which is prepared by chloromethylating a highly cross-linked copolymer of styrene and divinylbenzene followed by treatment of the chloromethylated material with a tertiary amine such as trimethylamine. To prepare an acid addition salt of this invention, for example, the citrate, the resin is first contacted with an aqueous solution of citric acid whereupon an anion exchange takes place converting the quaternary halide to the citrate. The citrate resin is then contacted with an acid addition salt prepared as described above and a further anion exchange takes place converting the acid addition salt to the citrate and leaving the anion of the original salt on the resin. The citrate resin can be recovered from the eluate by a number of methods such as evaporation or solvent precipitation. This same procedure can be used to prepare nitrates, sulfates, acetates and other acid addition salts.

The agents of this invention may be administered alone but are generally administered with a pharmaceutical carrier. selectedon the bas s of the chosenroute of adminis:

tration and standard pharmaceutical practice. For ex ample, they may be administered orally in the form of tablets or capsules containing such excipients as starch, milk sugar, certain types of clay, etc. They may be administered orally in the form of elixirs or oral suspensions which may contain coloring and flavoring agents. They may be injected parenterally and for this use may be prepared in the form of sterile aqueous solutions containing other solutes such as saline or glucose in sufiicient quantity to make the solution isotonic. For intramuscular administration compositions of the compounds of this invention may be prepared in an oil base such as peanut or sesame oil.

The compounds of this invention are central nervous system regulators and are useful in the same manner as other regulators of the central nervous system. The dosage is generally of the same order of magnitude as the dosage required with other therapeutic agents of this type.

In certain instances it may be found that because of their high order of activity the optimum dosage of the compounds of this invention will be lower than the optimum dosage of other compounds generally recommended for the same use. In general, the physician or veterinarian will determine the dosage which will be most suitable for a particular application, and as might be expected, it will vary with the particular drug chosen and with the desired effect. It will vary with the age, weight and general health of the patient under treatment and with various other factors which will be determined by the physician or veterinarian in attendance. When the drugs are administered orally a larger quantity will be required to produce the same effect as a smaller quantity given parenterally. It has been found that parenteral administration of from 0.5 mg. to 250 mg. of active agent generally gives the desired effect. The compositions of this invention may take a variety of, forms. Various diluents may be employed and the percentage of active ingredients maybe varied. It is necessary that an active ingredient form a proportion of the composition suchthat a suitable dosage form will be obtained. Obviously compositions with less than 0.005% by weight of active ingredient are suitable, it is preferred to use compositions containing not less than 0.005 of the active agent because otherwise the amount of carrier becomes excessively large. Activity increases with the concentration of the active agent. The percentage by weight of active agent may be 10, 50, 75, 95% or even higher. Dosage unit forms may be prepared with a minor proportion of a carrier and a major proportion of active materials and vice-versa.

The following examples are given solely for the purpose of illustration and are not to be construed as limitations of this invention, many variations of which are possible Without departing from the spirit or scope thereof.

EXAMPLE I f N-(I-indanyl)-N'-,3-br0moethyl urea A solution of 0.05 mole of B-bromoethyl isocyanate dissolved in 25 ml. of ether is added slowly with stirring to an ether solution of 0.05 mole of l-indanylamine under anhydrous conditions while cooling in an ice bath. Crystallization begins during the addition of the isocyanate and continues while the solution stands for one hour. The suspension is filtered to obtain the desired product.

EXAMPLE II 2-( 1 -inda nylamino) -oxazoline One liter (1 l.) of water is brought to boiling and 15 g. of N-( l-indanyl)-N-fi-bromoethyl urea is added. At the end of fifteen minutes reflux time all except a very small amount of material dissolves. The flask is cooled in an ice bath and the small amount of insoluble material along with an additional quantity of material which separates on cooling is removed by filtration. A 14% solution'of ammonium hydroxide (30 ml. is added slowly. The precipitate is extracted with three 250 ml. portions of chloroform and the combined extract washed with water. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue is triturated with ether and recrystallized from isopropanol.

EXAMPLE III N -(2-chl0r0-1 -indanyl) -N '-,B-chl0roethyl urea A solution of 0.5 of ,B-chloroethyl isocyanate in 50ml. of benzene is added with stirring to a 0.4 molar solution of 2-chloro-1-indanylamine in benzene while maintaining the temperature below 50 C. Stirring is continued at this temperature for an additional twenty minutes and the solution is cooled. The product precipitates on cool ing and is isolated by filtration.

EXAMPLE IV 2- (Z-chloro-I-indanylamino) -0xazoline One liter of water is brought'to boiling and 15 g. of N-(2-chloro-l-indanyl)-N'-;8-chloroethyl urea is added. The solution is refluxed for fifteen minutes, cooled and filtered. It is neutralized with 14% ammonium hydroxide and the precipitate which forms extracted with three 250 ml. portions of chloroform. The combined extracts are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crystalline residue which forms is triturated with ether and recrystallized. I

EXAMPLE V N- (3,4-dimethyl-1-indanyl) -N'-fi-chloroethyl urea A solution of ice cold 50% potassium hydroxide (150 g.) is shaken with a suspension of 0.6 mole of chloroethylamine hydrochloride in 420 ml. of benzene. The benzene layer containing the free base is precipitated and dried over a small amount of potassium hydroxide. The drying agent is removed by filtration. To this solution an equimolar benzene solution of 3,4-dimethyl-1-indanyl isocyanate is added dropwise with cooling. The solution is allowed to stand for one hour during which time the product separates.

EXAMPLE VI 2-(3,4-dimelhyl-1-indanylamin0)-0xaz0line One liter of water is brought to boiling and 15 g. of N (3,4 dimethyl l-indanyl)-N-p-chloroethyl urea is added. The solution is refluxed for fifteen minutes, cooled and filtered. A 10% solution of sodium hydroxide is added slowly and the precipitate which forms extracted with three 250 ml. portions of chloroform. The combined extracts are washed with water and the organic layer dried over anhydrous sodium sulfate. The solvent is concentrated in vacuo and the residue which forms is triturated with ether and recrystallized.

EXAMPLE VII N 2,5 -dii0d0-1 -indanyl -N 8- p-toluen esulfonyloxy ethyl urea A solution of 0.25 mole of fl-(p-toluenesulfonyloxy} ethyl isocyanate in ethylene dichlorideis added with stirring to an ethylene dichloride solution of an equimolar proportion of 2,5-diiodo-1-indanylamine while the temperature is maintained below C. When addition is completed, the solution is allowed to cool and the desired product precipitates. It is recovered by filtration.

EXAMPLE VIII 2-(2,5-dii0do-1indanylamino)-oxazoline One liter of water is brought to boiling. and 15 g. of N (2,5 diiodo 1 indanyl) N B (p toluenesulfonyloxy)-ethyl urea is added. The solution is refluxed for fifteen minutes, cooled and filtered. A 5% solution of sodium bicarbonate is added and the precipitate which forms is extracted with three 250 ml. portions of chloroform. The combined extracts are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue which forms is triturated with ether and recrystallized.

EXAMPLE IX N-(3,5-dithipropyl I indanyl)-N-fi-methyl-fi-chloro)- ethyl urea A solution of ice cold 50% potassium hydroxide (150 g.) is shaken with a suspension of 0.6 mole of 3,5-dithiopropyl-l-indanylamine hydrochloride in 420 ml. of benzene. The benzene layer containing the free base is separated and dried over a small amount of potassium hydroxide. The drying agent is removed by filtration. To this solution is added dropwise with cooling, an equimolar benzene solution of fl-chloropropyl isocyanate. The solution is allowed to stand for one hour during which time the product separates.

EXAMPLE X 2-(3,5-dithi0propyl-1-indanylamine)-5-methyl oxazoline One liter of water is brought to boiling and 15 g. of N-(3,5-dithiopropyl-l-indanyl)-N-chloropropyl urea is added. The. solution is refluxed for fifteen minutes, cooled and filtered. It is neutralized with 10% ammonium hydroxide solution and the precipitate which forms extracted with three 250 ml. portions of chloroform. The combined extracts are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crystalline residue which forms is triturated with ether and recrystallized.

EXAMPLE XI N-(1 -indanyl) -N '-fl-chl0r0ethyl urea A solution of 1.17 g. of B-chloroethyl isocyanate dissolved in 25 ml. of ether is slowly added with stirring to an equimolar ether solution of l-indanylamine under anhydrous conditions while cooling in an ice bath. Crystallization begins during the addition of the isocyanate and continues while the solution stands for one hour. The suspension is filtered to obtain the desired product.

EXAMPLE XII N 1 -indanyl -N '-fl-i0a 0ethyl urea A solution of p-iodoethyl isocyanate dissolved in. ether is slowly added with stirring to an ether solution of 1- indanylamine under anhydrous conditions while cooling in an ice bath. Crystallization begins. during the addition of the isocyanate and continues while the solution stands for one hour. The suspension is filtered tov obtain the desired. product.

EXAMPLE XIII N -(1 -indanyl -N S-n-butyl-fi-chloro) -ethyl area A solution of ice cold 50% potassium hydroxide (150 g.) is shaken with a suspension of 0.6 mole of l-indanylamine hydrochloride in 420 ml. of benzene. The benzene layer containing the free base is separated and dried over a small amount of potassium hydroxide. The drying agent is removed by filtration. To this solution an equimolar benzene solution or B-chlorohexyl isocyanate is added dropwise with cooling. The solution is allowed to stand during which time the desired product separates.

EXAMPLE XIV 2- (1 -indanylamino) -5-n-butyl oxazoline One liter of water is brought to boiling and 15 g. of N-(fl-n-butyl-fl-chloro)ethy1 urea is added. The solution is refluxed for fifteen minutes, cooled and filtered. The solution is. made basic with a 14% solution of ammonium hydroxide and, the precipitate which forms extracted with three 250 m1. portions of chloroform. The combined extracts are washed with water. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Crystalline residue which forms is triturated with ether and recrystallized.

EXAMPLE XV N Z-melhyl-I -indanyl) -N '-;8-methan esulfony loxy ethyl urea A solution of ice cold 50% potassium hydroxide g.) is shaken with a suspension of 0.6 mole of S-methyl-lindanylamine hydrochloride in 420 ml. of benzene. The benzene layer containing the free base is separated and dried over a small amount of potassium hydroxide. The drying agent is removed by filtration. To this solution an equimolar benzene solution of fl-(methanesulfonyloxy)-ethyl isocyanate is added dropwise with cooling. The solution is allowed to stand for one hour during which time the product precipitates.

EXAMPLE XVI Z-(Z-methyl-J -indanylamin0)-oxaz0line One liter of water is brought to boiling and 15 g. of N-( 8-methy1-1-indanyl) -N'- (fi-(methanesulfonyloxy ethyl urea is added. The solution is refluxed for fifteen minutes, cooled and filtered. The solution is neutralized with 10% sodium hydroxide and the precipitate which forms extracted with three 250 ml. portions of chloroform. The combined extracts are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crystalline residue which forms is triturated with ether and crystallized.

EXAMPLE XVII 2- ('1 -indrmylamino) -oxaz0line sulfate A 15% aqueous solution of 2.-(1-indanylamino)-oxazoline hydrochloride is stirred for three hours with an anion exchange. resin which had been previously washed with an aqueous sulfuric acid. The resin was removed by filtration and the solvent removed in vacuo to leave the sulfuric acid addition salt as a residue.

Included among the anion exchange resins used for this process was Amberlite IRA-410 and Amberlite IRA- 400 available from Rohm & Haas Company, as well as Dowex-l and Dowex-Z available from the Dow Chemical Company.

A number of other acid addition salts are prepared using this procedure and these include the acetate, citrate, malerate, gluconate, nitrate, tartrate and phosphate.

EXAMPLE XVIII A tablet base is prepared by blending the following ingredients in the proportion by weight indicated:

Grams Sucrose U.S.P 82.0

Tapioca starch 13.6 Magnesium stearate 4.4

Into this tablet there is blended a sufficient amount of N-( 1-indanyl)-N'-( B-ethyl-B-chloro) -ethyl urea to provide tablets each containing 25 mg. of active ingredient.

EXAMPLE XIX A. tablet base is prepared by blending the following ingredients in the proportion by weight indicated:

Grams Sucrose U.S.P. 80.3 Tapioca starch 13.2 Magnesium stearate 6.5

Into this base there is blended a sufficient amount of N-(l-indanyl)-N-fl-(methanesulfonyloxy)-ethyl urea to provide tablets each containing 50 mg. of active ingredient.

EXAMPLE XXI An aqueous solution containing 0.005% by weight of 2-(1-indanylamino)-4-methy1 oxazoline hydrobrqmide is prepared by dissolving the salt in U.S.P. distilled water.

EXAMPLE XXIII Sesame oil is sterilized by heating at 120 C. for two hours. To this oil a sufiicient quantity of pulverized N-(l-indanyl)-N'-p-iodo ethyl urea is added to make a 0.025% suspension by weight. The solid is thoroughly dispersed in the oil with the use of a colloid mill. It is then filtered through a 100 to 150 mesh screen and poured into sterile vials.

What is claimed is:

1. A compound selected from the group consisting of substituted and unsubstituted N-(l-indanyl)-N-(p-substituted ethyl)-ureas wherein (a) the substituents on a substituted indanyl ring are selected from the group consisting of one to three alkyl, alkoxy and thioalkyl groups each containing up to four carbon atoms, and one to three chlorine, bromine and iodine atoms; (b) the [3 substituent on the ethyl group of said urea is selected from the group consisting of bromine, chlorine and iodine atoms and methanesulfonyloxy and p-toluenesulfonyloxy groups, and (c) each substituent on a substituted carbon atom of said ethyl group is selected from the group consisting of alkyl groups containing up to four carbon atoms and the total number of carbon atoms in said substituents is from one to eight carbon atoms.

2. A process for the preparation of an N-(1-indanyl)- N-( 8-substituted alkyl)-urea which comprises reacting an isocyanate with an amine, said isocyanate being a 1- indanyl isocyanate when said amine is a fl-substituted alkylamine and said isocyanate being a p-substituted alkyl isocyanate when said amine is a l-indanylamine, the {3- substituents on said B-substituted alkylamine and B-substituted alkyl isocyanate beign selected from the group consisting of bromine, chlorine and iodine atoms and methanesulfonyloxy and p-toluenesulfonyloxy groups.

3. N-(l-indanyl)-N'-;8-bromoethyl urea.

4. N-(2-chloro-1-indanyl)-N'-;9-chloroethyl urea.

5. N-(3,4-dimethyl-1-indanyl)-N-Bchloroethyl urea.

6. N-(2,5-diiodo 1- indanyl)-N-/3-(p-toluenesulfonyloxy)-ethyl urea.

7. N-(3,5-dithiopropyl 1 indanyl) N'-p-methyl-pchloroethyl urea.

No references cited. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF SUBSTITUTED AND UNSUBSTITUTED N-(1-INDANYL)-N''-(B-SUBSTITUTED ETHYL)-UREAS WHEREIN (A) THE SUBSTITUENTS ON A SUBSTITUTED INDANYL RING ARE SELECTED FROM THE GROUP CONSISTING OF ONE TO THE THREE ALKYL, ALKOXY AND THIOALKYL GROUPS EACH CONTAINING UP TO FOUR CARBON ATOMS AND ONE TO THREE CHLORINE, BROMINE AND IODINE ATOMS; (B) THE B SUBSTITUENT ON THE ETHYL GROUP OF SAID UREA IS SELECTED FROM THE GROUP CONSISTING OF BROMINE, CHLORINE AND OIDINE ATOMS AND METHANESULFONYLOXY AND P-TOLUENESULFONYLOXY GROUPS, AND (C) EACH SUBSTITUENT ON A SUBSTITUTED CARBON ATOM OF SAID ETHYL GROUP IS SELECTED FROM THE GROUP CONSISTING OF ALKYL GROUPS CONTAINING UP TO FOUR CARBON ATOMS AND THE TOTAL NUMBER OF CARBON ATOMS IN SAID SUBSTITUENTS IS FROM ONE TO EIGHT CARBON ATOMS.
 6. N-(2,5-DIIODO - 1 - INDANYL)-N''-B-(P-TOLUENESULFONYLOXY)-ETHYL UREA. 